Results
Study sample – a total of 74 survivors, almost all of them white
Caucasian, formed the study sample. These subjects (40 males and 44 with
standard risk [SR] ALL) were 13.5 – 38.3, median 21.1 years of age
at the time of participation and 10.2 – 26.3, median 15.1 years from
diagnosis. High risk (HR) disease was defined by any one of the
following – age > 10 years, WBC >
50x199 /L, T cell phenotype, CNS involvement,
mediastinal mass and t(9;22) translocation. The majority of the subjects
(n=51, 69%) had received cranial irradiation, reflecting the era in
which they were treated. All of the subjects underwent DXA and all but
two had pQCT examination.
Total and trabecular BMC and trabecular vBMD were much lower at the
(non-weight bearing) radial metaphysis than at the tibial metaphysis
(Table 1), as in healthy subjects (Supplementary Tables 1 and 2) with
which these values are closely similar. Cortical BMC and vBMD at the
diaphyseal sites in both bones (Table 1) are also similar to published
values (Supplementary Tables 1 and 2). Data from healthy subjects for
cortical thickness are limited, with only one publication each at the
20% radius19 and 38% tibia,21 and
two at the 66% tibia (Supplementary Tables 1 and
2).16,23 The mean values for this metric in the study
sample were approximately the same as these published data; 2.33 v 2.7,
4.95 v 5.0 and 3.79 v 4.1 mm at the 20% radius, 38% tibia and 66%
tibia respectively. Published data for polar SSI are even more limited,
with none at the 38% tibia. Polar SSI values at the 20% radius and
66% tibia in the study sample (Table 1) are quite similar to the
published values (Supplementary Tables 1 and
2).15,18,22 Polar SSI, a measure of bone strength
(resistance to bending and twisting), and combining geometry and
density, was progressively higher in the diaphyseal shafts with
increasing distance from the distal metaphyses at the wrist and ankle
(Table 1). The Z scores provided by comparison with the reference
population are given in Table 2 and reveal a different picture of the
health of both metaphyseal and diaphyseal bone.
The metrics from post-processed images are displayed in Supplementary
Table 3. Striking and highly significant differences were evident
between males and females at the metaphyseal sites (Table 3). These
differences were seen in the non-weight bearing radius but not in the
weight bearing tibia, although the directionality was the same; males
had greater BMC and vBMD with improved architecture – smaller average
and maximum hole sizes with fewer free ends and isolated points, and so
higher connectivity. Likewise, apparent trabecular thickness and number
were higher in males.
A different profile was seen at all of the diaphyseal sites (Table 3).
Males had significantly greater total and cortical BMC but females had
higher total vBMD, though this was not statistically significant, and
there were significantly higher values in cortical vBMD for females,
probably reflecting their lower cortical thickness. Most importantly,
the polar SSI (a measure of bone strength) was significantly greater in
males than in females at all diaphyseal sites.
There were no significant differences in any of the metrics at
metaphyseal sites related to age at examination. The only metric which
revealed a statistically significant difference at the diaphyseal sites
was cortical vBMD – at all three sites. The subjects were divided into
those 13-20 (N=30) and those > 20 years of age (N=42) and
the younger group had lower values (20% radius 1141.3 [55.7] vs
1218.3 [39.8], p<0.0001; 38% tibia 1149.7 [48.4] vs
1203.5 [22.2]. p<0.0001; 66% tibia 1089.5 [44.5] vs
1129.2 [26.6], p<0.0001. This may relate to a smaller
proportion of the younger subjects having attained peak bone mass.
With respect to ALL risk category, which is confounded by age at
diagnosis – children 10 years of age and older are automatically high
risk – there were no significant differences in BMC or vBMD, total or
trabecular, at the metaphyseal sites between subjects who were SR and
those HR at diagnosis, with the exception of Trabecular vBMD at the 4%
radius, but there were notable differences in apparent bone architecture
(Table 4). The SR group had smaller average and maximum hole sizes with
fewer free ends and isolated points and so higher connectivity.
Likewise, at both the 4% radius and 4% tibia the trabecular number was
higher in SR than in HR subjects, reflecting more compact bone. At the
diaphyseal sites there were statistically significant differences only
with cortical vBMD; the HR subjects (N=29) having slightly higher values
than those who had SR disease (20% radius 1204.7 [52.8] vs 1173.8
[62.5], p=0.032; 38% tibia 1193.6 [43.9] vs 1172.7 [48.1],
p=0.048; 66% tibia 1125.4 [28.0] vs 1104.4 [44.7], p=0.028),
with no differences in cortical thickness.
There were no statistically significant differences in any of the
metrics at any of the sites between subjects with (N=27) and those
without (N=45) a history of fracture (two missing data), nor between
those who had received a bisphosphonate (N=14) and those who had not
(N=58); two missing data. No differences were observed between those who
had (N=49) and those who had not (N=23) received cranial irradiation
(two missing data) with respect to the metaphyseal bone metrics. At the
diaphyseal sites there were no consistent differences between irradiated
and non-irradiated subjects.